Periodontal disease is a major cause of tooth loss in humans, and it is becoming a more important oral health problem as dental caries is being brought under control. It is caused by the interaction of bacteria and their products with host defense systems, resulting in formation of pockets and destruction of the periodontal ligament and bone. Regeneration of damaged connective tissue and restoration of its attachment to the tooth root are major therapeutic goals. We suggest that factors present in normal tooth root cementum guide and regulate the cells that generate and regenerate the periodontal ligament and cementum. We have identified polypeptides in cementum which promote the growth and attachment of periodontal fibroblasts, and isolated a growth factor which appears to be different from other known growth factors. This growth factor has been purified. We have obtained a human cementum tumor cell line that produces this growth factor, and propagated it in culture. We have constructed a cDNA library using mRNA obtained from the cementum tumor cells. We will screen the library with oligonucleotide and antibody probes, and clone the cDNA for this cementum-derived growth factor. We will define the structure of the growth factor based on DNA and amino acid sequences, and express the cDNA in cells to produce the growth factor in vitro. The effect of this growth factor on growth and differentiation of periodontal cells will be studied and receptors identified. We will use the cDNA probes to examine periodontal and other tissues by in situ hybridization to identify cells and tissues producing the growth factor and to determine how its production is regulated during tooth development. The effect of mediators of inflammation on growth factor synthesis will be evaluated in cementum cell cultures. Finally, we will study the distribution of this growth factor in diseased states. From these studies we expect to elucidate the molecular structure and function of the cementum-derived growth factor to understand how this growth factor may participate in cementum formation and in periodontal connective tissue formation and reattachment. We expect that the knowledge gained will help to design rational procedures to form new cementum and reestablish connective tissue attachment to root surfaces.